Amphiphilic amino acid and peptide derivatives have surfactant properties that make then utilizable, alone or with other substances, as emulsifiers or co-emulsifiers, as dispersants or solubilizers, as modifiers of natural or synthetic membranes or in forming drug vehicles or targeting devices. Some of them are capable of forming vesicles (a structure equivalent to that of the liposomes obtained from phospholipids).
A drug vehicle provides advantages in therapy, among them prolonged intravascular persistence and a controlled release of the drug, resulting in greater efficacy and reduced doses, which is of great importance when the drug is toxic or provokes side effects. The pharmacokinetics and biodistribution of the encapsulated drug are determined by the drug vehicle, and thus on the structure of the molecules that compose this vesicle. Thus, in order to enhance the specificity of the vesicles for targeting cells, derivatives of carbohydrates are incorporated in vesicles containing an imaging agent or a therapeutic agent (see Liposome Technology, Targeted Drug Delivery and Biological Interaction, Vol. III, G. Gregoriadis ed., CRC Press, Inc., 1984).
The present invention deals with new amphiphiles that can be used as drug vehicles and for the specific targeting of a drug by virtue of a terminal sugar group which is recognized by specific receptor on the cell membrane. The new amphiphiles comprise a carbohydrate part and a peptidic spacer between the hydrophilic saccharidic head and the hydrocarbon and/or fluorocarbon hydrophobic tail. Hydrocarbon molecules with a sugar head have been described by Okahaya et al. (J. Chem. Soc. Perkins Trans. 2 (1987) p. 1317), but they do not bear a peptidic spacer. Amphiphilic compounds derived from sugars and bearing a fluorocarbon chain, but with no peptidic spacer, have been described in EP-A-0255443. In the amphiphilic compounds of the invention, the peptidic spacer allows the modulation of the hydrophilic/lipophilic balance of the molecule and thus contributes to determining the structure of the dispersion obtained.
The amphiphilic compounds of the invention can also be used as emulsifiers or co-emulsifiers, as for example in oxygen-transport systems based on fluorocarbons. Such systems presently exist, but they present certain disadvantages, specifically, the surfactants used are not particularly adapted to the emulsification of fluorocarbons, and do not allow modification of the characteristics of the emulsions in order to adapt them to specific therapeutic applications.
The present invention has as its specific object amphiphile derivatives of amino acids of peptides, suitable in particular for the fixation, dispersion, encapsulation and targeting of pharmaceutical products and the emulsification of fluorocarbons.